This project will characterize peptidergic transmission in bullfrog sympathetic ganglia, as a model system for the slow, modulatory action of peptides in the nervous system. The actions of peptides, particularly T-LHRH (the luteinizing hormone-releasing hormone of the teleost fish) and substance P, will be studied on individual cells of the ganglia under voltage clamp. The inhibitory action of peptides on the M-current, a novel voltage-dependent potassium current, will be investigated. Synaptic potentials resulting from the action of peptides, including the late, slow EPSP, will be studied. Other peptides, which may be present in the ganglia, will be tested for pre- or postsynaptic effects, and for modulatory effects on the acetylcholine receptors of ganglion cells. The chemical nature of the peptides present in the ganglion will be determined by high performance liquid chromatography, and possibly amino acid analysis and sequencing. Enzymatic degradation of peptides, and its possible role in the physiological action of the peptides, will be examined. The receptors for T-LHRH and substance P will be identified by in vitro binding studies, and will be located in the ganglia by autoradiography. This multidisciplinary approach should increase our understanding of the fundamental mechanisms involved in the generation of peptidergic synaptic actions in the nervous system.